Method for producing triazolinthion derivatives

ABSTRACT

According to a novel process, it is possible to prepare triazolinethione derivatives of the formula                    
     in which 
     R 1  and R 2  are each as defined in the description by 
     a) reacting hydrazine derivatives of the formula                    
     or their acid addition salts with an inorganic or organic acid 
     with thiocyanate of the formula 
     
       
         Y—SCN  (III) 
       
     
     in which 
     Y represents sodium, potassium or ammonium 
     in the presence of a diluent and, if appropriate, in the presence of a catalyst and 
     b) reacting the resulting thiosemicarbazide derivatives of the formula                    
     with formic acid, if appropriate in the presence of a catalyst and if appropriate in the presence of a diluent. 
     The thiosemicarbazide derivatives of the formula (IV) are novel. Method for producing triazolinthion derivatives

The present invention relates to a novel process for preparingtriazolinethione derivatives which are known as active compounds havingmicrobicidal, in particular fungicidal, properties.

It is already known that triazolinethione derivatives can be prepared byeither reacting the corresponding triazole derivatives successively withstrong bases and sulphur and then hydrolysing them, or reacting themdirectly with sulphur at high temperatures, followed by treatment withwater (cf. WO-A 96-16 048). However, this process has the disadvantagethat the desired products are obtained in only relatively low yields, orthat reaction conditions are required which are difficult to maintain onan industrial scale.

Furthermore, it has already been described that certain1,2,4-triazoline-5-thiones substituted in the 3 position can be preparedby reacting N-chlorothiofomiyl-N-(1-chloroalk-1-ene)-amines withcarbonylhydrazine derivatives (cf. DE-A 197 01 032, DE-A 196 01 189 andEP-A 0 784 053). However, the synthesis of corresponding substanceswhich do not have a substituent in the 3 position is not mentioned.

Furthermore, Bull. Chem. Soc. Japan 46, 2215 (1973) discloses thattriazolinethiones substituted in the 3 position can be synthesized byreacting phenylhydrazine with sodium thiocyanate and ketones oraldehydes in the presence of hydrochloric acid and treating theresulting triazolidenethiones substituted in the 3 position withoxidizing agents. This process has the disadvantages that very longreaction times are required and that no triazolinethiones which areunsubstituted in the 3 position can be obtained in this manner.

Finally, it is also known that2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(1,2,4-triazol-1-yl)-propan-2-oleis obtained when[1-(2-chloro-phenyl)-2-(1-chloro-cyclopropyl)-2-hydroxy]-propyl-1-hydrazineis reacted with formamidine acetate (cf. DE-A 40 30 039). However,thiono derivatives of triazoles are not obtainable by this method.

It has now been found that triazolinethione derivatives of the formula

in which

R¹ and R² are identical or different and each represents optionallysubstituted alkyl, optionally substituted alkenyl, optionallysubstituted cycloalkyl, optionally substituted aralkyl, optionallysubstituted aralkenyl, optionally substituted aroxyalkyl, optionallysubstituted aryl or optionally substituted heteroaryl,

can be prepared by

a) reacting, in a first step, hydrazine derivatives of the formula

in which

R¹ and R² are each as defined above,

or their addition salts with an inorganic or organic acid,

with thiocyanate of the formula

Y—SCN  (III)

in which

Y represents sodium, potassium or ammonium,

in the presence of a diluent and, if appropriate, in the presence of acatalyst, and

b) reacting the resulting thiosemicarbazide derivatives of the formula

in which

R¹ and R² are each as defined above

with formic acid, if appropriate in the presence of a catalyst and ifappropriate in the presence of a diluent.

It is extremely surprising that the triazolinethione derivatives of theformula (I) can be prepared by the process according to the invention insubstantially higher yields or under considerably more simple conditionsthan by the prior-art methods. It is likewise unexpected that, in thepractice of the first step of the process according to the invention,the attack of the thiocyanate occurs predominantly not at the terminalbut at the substituted nitrogen atom of the hydrazine derivative of theformula (II), thus yielding the desired isomer with high selectivity.

The process according to the invention has a number of advantages. Thus,as already mentioned, it is possible to synthesize triazolinethionederivatives of the formula (I) in high yield. It is also favourable thatthe required starting materials and reaction components can be preparedin a simple manner and are available even in relatively large amounts. Afurther advantage consists in the fact that the individual steps can becarried out and the reaction products can be isolated without anyproblems. Using 2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydrazoniumsulphate as starting material and reacting this in the first step withammonium thiocyanate and allowing the resulting thiosemicarbazide toreact in the second step with formic acid, the course of the processaccording to the invention can be illustrated by the scheme below.

The formula (II) provides a general definition of the hydrazinederivatives required as starting materials for carrying out the processaccording to the invention. Preference is given to using compounds ofthe formula (II) in which

R¹ represents straight-chain or branched alkyl having 1 to 6 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting ofhalogen, alkoxy having 1 to 4 carbon atoms, alkoximino having 1 to 4carbon atoms in the alkoxy moiety and cycloalkyl having 3 to 7 carbonatoms,

or

represents straight-chain or branched alkenyl having 2 to 6 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting ofhalogen, alkoxy having 1 to 4 carbon atoms and cycloalkyl having 3 to 7carbon atoms,

or

represents cycloalkyl having 3 to 7 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, cyano and alkylhaving 1 to 4 carbon atoms,

or

represents aralkyl having 6 to 10 carbon atoms in the aryl moiety and 1to 4 carbon atoms in the straight-chain or branched alkyl moiety, wherethe aryl moiety may in each case be mono- to trisubstituted by identicalor different substituents from the group consisting of halogen, alkylhaving 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthiohaving 1 to 4 carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and1 to 5 identical or different halogen atoms, halogenoalkoxy having 1 or2 carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phienyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

represents aralkenyl having 6 to 10 carbon atoms in the aryl moiety and2 to 4 carbon atoms in the alkenyl moiety, where the aryl moiety may ineach case be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

represents aroxyalkyl having 6 to 10 carbon atoms in the aryl moiety and1 to 4 carbon atoms in the straight-chain or branched oxyalkyl moiety,where the aryl moiety may in each case be mono- to trisubstituted byidentical or different substituents from the group consisting ofhalogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbonatoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, halogenoalkylthio having 1 or 2 carbon atomsand 1 to 5 identical or different halogen atoms, cycloalkyl having 3 to7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbonatoms in the alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atomsin the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitroand cyano,

or

represents aryl having 6 to 10 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

represents an optionally benzo-fused 5- or 6-membered heteroaromaticradical having 1 to 3 heteroatoms, such as nitrogen, sulphur and/oroxygen, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting ofhalogen, alkyl having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4carbon atoms, hydroxyalkinyl having 3 to 8 carbon atoms, alkoxy having 1or 2 carbon atoms, alkylthio having 1 or 2 carbon atoms, halogenoalkyl,halogenoalkoxy and halogenoalkylthio having in each case 1 or 2 carbonatoms and 1 to 5 identical or different halogen atoms, such as fluorineor chlorine atoms, formyl, dialkoxymethyl having 1 or 2 carbon atoms ineach alkoxy group, acyl having 2 to 4 carbon atoms, alkoxycarbonylhaving 1 to 4 carbon atoms in the alkoxy moiety, alkoximinoalkyl having1 to 4 carbon atoms in the alkoxy moiety and 1 to 3 carbon atoms in thealkyl moiety, nitro and cyano, and

R² represents straight-chain or branched alkyl having 1 to 6 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting ofhalogen, alkoxy having 1 to 4 carbon atoms, alkoximino having 1 to 4carbon atoms in the alkoxy moiety and cycloalkyl having 3 to 7 carbonatoms,

or

represents straight-chain or branched alkyl having 2 to 6 carbon atoms,where each of these radicals may be mono- tb trisubstituted by identicalor different substituents from the group consisting of halogen, alkoxyhaving 1 to 4 carbon atoms and cycloalkyl having 3 to 7 carbon atoms,

or

represents cycloalkyl having 3 to 7 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, cyano and alkylhaving 1 to 4 carbon atoms,

or

represents aralkyl having 6 to 10 carbon atoms in the alkyl moiety and 1to 4 carbon atoms in the straight-chain or branched alkyl moiety, wherethe aryl moiety may in each case be mono- to trisubstituted by identicalor different substituents from the group consisting of halogen, alkylhaving 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthiohaving 1 to 4 carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and1 to 5 identical or different halogen atoms, halogenoalkoxy having 1 or2 carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

represents aralkenyl having 6 to 10 carbon atoms in the aryl moiety and2 to 4 carbon atoms in the alkenyl moiety, where the aryl moiety may ineach case be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, 5 halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

represents aroxyalkyl having 6 to 10 carbon atoms in the aryl moiety and1 to 4 carbon atoms in the straight-chain or branched oxyalkyl moiety,where the aryl moiety may in each case be mono- to trisubstituted byidentical or different substituents from the group consisting ofhalogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbonatoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkoxy having 1 or 2 carbon atoms and I to 5 identical ordifferent halogen atoms, halogenoalkylthio having 1 or 2 carbon atomsand 1 to 5 identical or different halogen atoms, cycloalkyl having 3 to7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbonatoms in the alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atomsin the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitroand cyano,

or

represents aryl having 6 to 10 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

represents an optionally benzo-fused 5- or 6-membered heteroaromaticradical having 1 to 3 heteroatoms, such as nitrogen, sulphur and/oroxygen, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting ofhalogen, alkyl having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4carbon atoms, hydroxyalkinyl having 3 to 8 carbon atoms, alkoxy having 1or 2 carbon atoms, alkylthio having 1 or 2 carbon atoms, halogenoalkyl,halogenoalkoxy and halogenoalkylthio having in each case 1 or 2 carbonatoms and 1 to 5 identical or different halogen atoms, such as fluorineor chlorine atoms, formyl, dialkoxymethyl having 1 or 2 carbon atoms ineach alkoxy group, acyl having 2 to 4 carbon atoms, alkoxycarbonylhaving 1 to 4 carbon atoms in the alkoxy moiety, alkoximinoalkyl having1 to 4 carbon atoms in the alkoxy moiety and 1 to 3 carbon atoms in thealkyl moiety, nitro and cyano.

Particular preference is given to using hydrazine derivatives of theformula (II) in which

R¹ represents straight-chain or branched alkyl having 1 to 4 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,alkoximino having 1 or 2 carbon atoms in the alkoxy moiety, cyclopropyl,cyclobutyl, cyclopentyl and cyclohexyl,

or

represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

represents cycloalkyl having 3 to 6 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,cyano, methyl, ethyl, propyl, isopropyl and tert-butyl,

or

represents phenylalkyl having 1 to 4 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, tri fluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents phenoxyalkyl having 1 to 4 carbon atoms in the straight-chainor branched oxyalkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenyl which may be mono- to trisubstituted by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoroniethoxy,chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano, formyl,dimethoxymethyl, acetyl and propionyl, and

R² represents straight-chain or branched alkyl having 1 to 4 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,alkoximino having 1 or 2 carbon atoms in the alkoxy moiety, cyclopropyl,cyclobutyl, cyclopentyl and/or cyclohexyl,

or

represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

represents cycloalkyl having 3 to 6 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,cyano, methyl, ethyl, propyl, isopropyl and tert-butyl,

or

represents phenylalkyl having 1 to 4 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, di fluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents phenoxyalkyl having 1 to 4 carbon atoms in the straight-chainor branched oxyalkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, tri fluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenyl which may be mono- to trisubstituted by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethythio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, I-methoximinoethyl, nitro and cyano, formyl,dimethoxymethyl, acetyl and propionyl.

Very particular preference is given to using hydrazine derivatives ofthe formula (II) in which

R¹ represents n-propyl, isopropyl, n-butyl, i-butyl, sec-butyl ortert-butyl, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,methoximino, ethoximino, cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl,

or

represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

represents 1-methyl-cyclohexyl, cyclohexyl, 1-chloro-cyclopropyl,1-fluorocyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,cyclopropyl, 1-methyl-cyclopentyl or 1-ethyl-cyclopentyl,

or

represents phenylalkyl having 1 or 2 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents phenoxyalkyl having 1 to 4 carbon atoms in the straight-chainor branched oxyalkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenyl which may be mono- to trisubstituted by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano, formyl,dimethoxymethyl, acetyl and propionyl, and

R² represents n-propyl, isopropyl, n-butyl, i-butyl, sec-butyl ortert-butyl, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,methoximino, ethoximino, cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl,

or

represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

represents 1-methyl-cyclohexyl, cyclohexyl, 1-chloro-cyclopropyl,1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,cyclopropyl, 1-methyl-cyclopentyl or 1-ethyl-cyclopentyl,

or

represents phenylalkyl having 1 or 2 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents phenoxyalkyl having 1 to 4 carbon atoms in the straight-chainor branched oxyalkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

represents phenyl which may be mono- to trisubstituted by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,chlorodifluoromethylthio, hydroxyrnethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano, formyl,dimethoxymethyl, acetyl and propionyl.

Preference is also given to using addition salts of the abovementionedpreferred or particularly preferred hydrazine derivatives of the formula(II) and an inorganic or organic acid. Preference is given tohydrazonium salts of the formula

in which

R¹ and R² are each as defined above and

X^(⊖) represents chloride or an equivalent of a sulphate anion.

The hydrazine derivatives of the formula (II) are known or can beprepared by processes known in principle (cf. DE-A 40 30 039).

Thus, hydrazine derivatives of the formula (II) are obtained by reacting1-chloro-2-hydroxy-ethane derivatives of the formula

in which

R¹ and R² are each as defined above

R¹ with hydrazine hydrate, if appropriate in the presence of a diluent.

The hydrazine derivatives of the formula (II) can be converted intotheir acid addition salts by reacting them with an inorganic or organicacid in the presence of a diluent.

The 1-chloro-2-hydroxy-ethane derivatives of the formula (V) are knownor can be prepared by processes known in principle (cf. DE-A 40 30 039and EP-A 0 297 345).

Suitable diluents for the above process for preparing hydrazinederivatives of the formula (II) are all customary inert organicsolvents. Preference is given to using alcohols, such as methanol,ethanol or n-butanol, furthermore ethers, such as dioxane or methyltert-butyl ether, and also aromatic hydrocarbons, such as benzene,toluene or xylene. However, it is also possible to carry out thereaction without any additional solvent. In this case, an excess ofhydrazine hydrate is employed, so that it acts both as reactioncomponent and as diluent.

When carrying out the preparation of hydrazine derivatives of theformula (II) according to the above process, the reaction temperaturescan be varied within a certain range. In general, the process is carriedout at temperatures between 60° C. and 120° C., preferably between 70°C. and 100° C.

In the preparation of hydrazine derivatives of the formula (II)according to the above process, in general from I to 20 mol, preferablyfrom 5 to 15 mol, of hydrazine hydrate are employed per mole of1-chloro-2-hydroxy-ethane derivative of the formula (V). Work-up iscarried out by customary methods. In general, the reaction mixture isadmixed with an organic solvent which is sparingly water-miscible, suchas methyl tert-butyl ether or toluene, the aqueous phase is removed andthe organic phase is washed and dried.

Suitable diluents for converting the hydrazine derivatives of theformula (II) into their acid addition salts are all organic solventswhich are customary for such reactions. Preference is given to usingaromatic hydrocarbons, such as benzene, toluene or xylene, or ethers,such as dioxane or methyl tert-butyl ether.

The hydrazine derivatives of the formula (II) are generally convertedinto salts at room temperature. However, it is also possible to carryout the conversion at a slightly elevated or reduced temperature.

The conversion of hydrazine derivatives of the formula (II) into saltsis generally carried out such that a hydrazine derivative of the formula(II) is dissolved in a solvent and mixed with an equivalent amount or anexcess of acid. When preparing chlorides, it is possible to use eitherhydrochloric acid or gaseous hydrogen chloride. The salts can beisolated by customary methods.

The thiocyanates of the formula (III) required as reaction componentsfor carrying out the first step of the process according to theinvention are known.

Suitable diluents for carrying out the first step of the processaccording to the invention are all inert organic solvents which arecustomary for such reactions. Preference is given to using aromatichydrocarbons, such as benzene, toluene. or xylene, Furthermore ethers,such as dioxane or methyl tert-butyl ether, and also esters, such asethyl acetate.

Suitable catalysts for carrying out the first step of the processaccording to the invention are all reaction promoters which arecustomary for such reactions. Preference is given to using water.

When carrying out the first step of the process according to theinvention, the reaction temperatures can be varied within a relativelywide range. In general, the reaction is carried out at temperaturesbetween 50° C. and 120° C., preferably between 70° C. and 110° C.

Both the first and the second step of the process according to theinvention are generally carried out under atmospheric pressure. However,it is also possible to carry out the process under elevated pressure or,if no gaseous components are involved in the reaction, also underreduced pressure.

When carrying out the first step of the process according to theinvention, in general from 1 to 2 mol of thiocyanate of the formula(III) and, if required, a small amount of catalyst are employed per moleof hydrazine derivative of the formula (II). Work-up is carried out bycustomary methods. In general, the reaction mixture is washed withwater, the organic phase is dried and concentrated and the residue thatremains is freed from undesirable components by customary methods, forexample by chromatography or recrystallization.

The formula (IV) provides a general definition of the thiosemicarbazidederivatives required as starting materials for carrying out the secondstep of the process according to the invention. In this formula, R¹ andR² each preferably have those meanings which have already been mentionedin connection with the description of the hydrazine derivatives of theformula (II) as being preferred for these radicals.

The thiosemicarbazide derivatives of the formula (IV) have hitherto notbeen known. They can be prepared by the reaction of the first step ofthe process according to the invention.

Suitable catalysts for carrying out the second step of the processaccording to the invention are all reaction promoters which arecustomary for such reactions. Preference is given to using acids, suchas hydrochloric acid or sulphuric acid, and furthermore metal oxides,such as amorphous titanium dioxide.

Suitable diluents for carrying out the second step of the processaccording to the invention are all weakly polar organic solvents whichare customary for such reactions. Preference is given to using esters,such as ethyl acetate or isobutyl formate, and also formic acid.

When carrying out the second step of the process according to theinvention, the reaction temperatures can be varied within a certainrange. In general, the reaction is carried out at temperatures between80° C. and 120° C., preferably between 90° C. and 110° C.

When carrying out the second step of the process according to theinvention, an excess, in general from 5 to 15 mol, of formic acid and,if required, a small amount of catalyst are employed per mole ofthiosemicarbazide derivative of the of the formula (IV). Work-up iscarried out by customary methods. In general, the reaction mixture is,if appropriate after prior dilution with an organic solvent that issparingly water-miscible, extracted with aqueous salt solution, and theorganic phase is dried and concentrated. Any impurities which may stillbe present can then be removed by customary methods, such asrecrystallization or chromatography.

In a particular variant, the process according to the invention can becarried out such that 1-chloro-2-hydroxy-ethane derivatives of theformula (V) are reacted with hydrazine hydrate and the resultinghydrazine derivatives of the formula (II) are then reacted furtherwithout prior isolation. Accordingly, triazolinethiones of the formula(I) can also be prepared by

reacting 1-chloro-2-hydroxy-ethane derivatives of the formula

in which

R¹ and R² are each as defined above

with hydrazine hydrate, if appropriate in the presence of a diluent, andreacting the resulting hydrazine derivatives of the formula

in which

R¹ and R² are each as defined above

if appropriate with an inorganic or organic acid in the presence of adiluent,

and reacting the hydrazine derivatives of the formula (II) or their acidaddition salts

without prior isolation with thiocyanate of the formula

Y—SCN  (III)

in which

Y represents sodium, potassium or ammonium

in the presence of a diluent and, if appropriate, in the presence of acatalyst and

reacting the resulting thiosemicarbazide derivatives of the formula

in which

R¹ and R² are each as defined above

with formic acid, if appropriate in the presence of a catalyst and ifappropriate in the presence of a diluent.

When carrying out the individual steps of this process, the procedurewhich has already been described above is adopted.

The triazolinethione derivatives preparable according to the inventioncan be present in the “thiono” form of the formula

or in the tautomeric “mercapto” form of the formula

For the sake of simplicity, only the “thiono” form is shown in eachcase.

The triazolinethione derivatives preparable according to the inventionare known as active compounds with microbicidal, in particularfungicidal, properties (cf. WO-A 96-16 048).

The practice of the process according to the invention is illustrated bythe examples below.

PREPARATION EXAMPLES EXAMPLE 1

a) Preparation of the Compound of the Formula

With stirring, a mixture of 4.86 g (15 mmol) of2-(1-chloro-cyclopropyl)-3-(2-chlorophenyl)-2-hydroxy-propyl-1-hydrazinium sulphate, 1.26 g (16.5 mmol) of ammonium thiocyanate and 30ml of ethyl acetate is heated between 74 and 76° C. for 3 hours. Thereaction mixture is then allowed to cool to room temperature and thenwashed with 20 ml of water. The organic phase is dried over sodiumsulphate, filtered and concentrated under reduced pressure. This gives5.81 g of a product which, according to HPLC analysis, comprises 65.9%of the thiosemicarbazide derivative of the formula (TV-1). Accordingly,the calculated yield is 76.4% of theory. After recrystallization frommethanol, the thiosemicarbazide derivative of the formula (IV-1) isobtained in the form of a crystalline solid which melts at from 128 to129° C.

b) Preparation of the Compound of the Formula

At room temperature, a mixture of 3.35 g (10 mmol) of thiosemicarbazidederivative of the formula (IV-1) in 10 ml of isobutyl formate is admixedwith stirring with 5 ml (132 mmol) of formic acid, and the mixture isthen heated at 95° C. for 5.5 hours. The reaction mixture is then cooledto room temperature and subsequently diluted with 50 ml of ethyl acetateand washed three times with 10 ml of saturated aqueous to ammoniumchloride solution each time. The organic phase is dried over sodiumsulphate, filtered and concentrated under reduced pressure. This gives3.65 g of a product which, according to HPLC analysis, comprises 86.4%of2-(1-chlorocyclopropyl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1 -yl)-propan-2-ole. Accordingly, the calculated yield is 91.6% oftheory.

COMPARATIVE EXAMPLES Example A

At −20° C., a mixture of 3.12 g (10 mmol) of2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-(l,2,4-triazol-1-yl)-propan-2-oleand 45 ml of absolute tetrahydrofuran is admixed with 8.4 ml (21 mmol)of n-butyl-lithium in hexane and stirred at 0° C. for 30 minutes. Thereaction mixture is then cooled to −70° C., admixed with 0.32 g (10mmol) of sulphur powder and stirred at −70° C. for 30 minutes. Themixture is warmed to −10° C., admixed with ice-water and adjusted to pH5 by addition of dilute sulphuric acid. The mixture is extractedrepeatedly with ethyl acetate, and the combined organic phases are driedover sodium sulphate and concentrated under reduced pressure. In thismanner, 3.2 g of a product which, according to gas chromatographicanalysis, comprises 95% of2-(1-chlorocyclopropyl)-1-(2-chloro-phenyl)-3-(4,5 -dihydro-1,2,4-triazol-5-thiono- 1-yl)-propan-2-ole are obtained.Recrystallization from toluene gives this substance as a solid whichmelts at from 138 to 139° C.

Example B

With stirring, a mixture of 3.12 g (10 mmol) of2-(l-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ole, 0.96 g (30 mmol)of sulphur powder and 20 ml of absolute N-methyl-pyrrolidone is heatedat 200° C. for 44 hours. The reaction mixture is then concentrated underreduced pressure (0.2 mbar). The resulting crude product (3.1 g) isrecrystallized from toluene. In this manner, 0.7 g (20% of theory) of2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-oleis obtained in the form of a solid which melts at from 138 to 139° C.

What is claimed is:
 1. A process for preparing a triazolinethionederivative of the formula (I)

in which R¹ and R² are identical or different and each representsoptionally substituted alkyl, optionally substituted alkenyl, optionallysubstituted cycloalkyl, optionally substituted aralkyl, optionallysubstituted aralkenyl, optionally substituted aroxyalkyl, optionallysubstituted aryl or optionally substituted heteroaryl, comprising a) ina first step, reacting a hydrazine derivative of the formula

in which R¹ and R² are each as defined above, or an addition saltthereof with an inorganic or organic acid, with a thiocyanate of theformula Y—SCN  (III) in which Y represents sodium, potassium orammonium, in the presence of a diluent, and b) reacting the resultingthiosemicarbazide derivative of the formula

in which R¹ and R² are each as defined above with formic acid.
 2. Theprocess according to claim 1, characterized in that the hydrazinederivative used is2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydraziniumsulphate having the formula


3. The process according to claim 1, characterized in that the reactioncomponent used for carrying out the first step is ammonium thiocyanate.4. The process according to claim 1, characterized in that the firststep is carried out at temperatures between 50° C. and 120° C.
 5. Theprocess according to claim 1, characterized in that the second step iscarried out at temperatures between 80° C. and 120° C.
 6. The process ofclaim 1 wherein the first step a) is conducted in the presence of acatalyst.
 7. The process of claim 1 wherein the second step b) isconducted in the presence of a catalyst, a diluent, or a mixturethereof.
 8. The process of claim 7 wherein step a) is conducted in thepresence of a catalyst.